Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy
S.-H. Li, Zhi‐Cheng Yao, Hanzhi Wang, Jonathan A. Ecker, Mary O. Omotoso, Judy J. Lee, Jiayuan Kong, Hexiang Feng, Worarat Chaisawangwong, Si-Sim Kang, Sydney R. Shannon, Natalie K. Livingston, Joan Glick Bieler, Shweta Singh, Maya L. Zhang, Pilar O’Neal, Emily Ariail, Benjamin Biggs, John W. Hickey, Hai‐Quan Mao, Jonathan P. Schneck
Abstract
Tissue-resident memory T (T RM ) cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. The lack of effective approaches for expanding T RM cells and delivering these cells in vivo hinders the exploration of T RM cell–mediated cancer immunotherapy. Here, we report a nanoparticle artificial antigen-presenting cell (nano-aAPC) ex vivo expansion approach and an in vivo delivery system for T RM cells. Using the nano-aAPC platform, we expanded functional antigen-specific murine and human T RM -like CD8 + T cells ex vivo. We also developed an injectable macroporous hyaluronic acid (HA) hydrogel to deliver T RM -like cells. T RM -like cells delivered in the optimized HA hydrogel trigger robust local and systemic antitumor immunity and show synergistic effects with anti–PD-1 treatment. Our findings suggest that nano-aAPC–induced T RM -like cells, coupled with a hydrogel delivery system, offer an efficient way to advance the understanding of T RM cell–mediated cancer therapy.